Loading…

Identification and validation of novel serum markers for early diagnosis of endometriosis

BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential...

Full description

Saved in:
Bibliographic Details
Published in:Human reproduction (Oxford) 2012-02, Vol.27 (2), p.408-417
Main Authors: Gajbhiye, R., Sonawani, A., Khan, S., Suryawanshi, A., Kadam, S., Warty, N., Raut, V., Khole, V.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43
cites cdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43
container_end_page 417
container_issue 2
container_start_page 408
container_title Human reproduction (Oxford)
container_volume 27
creator Gajbhiye, R.
Sonawani, A.
Khan, S.
Suryawanshi, A.
Kadam, S.
Warty, N.
Raut, V.
Khole, V.
description BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. METHODS A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. RESULTS The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. CONCLUSIONS Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.
doi_str_mv 10.1093/humrep/der410
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_916530070</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/humrep/der410</oup_id><sourcerecordid>916530070</sourcerecordid><originalsourceid>FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</originalsourceid><addsrcrecordid>eNqF0D1PwzAQBmALgWgpjKwoC4Il9OzYTjKiio9KlVhgYIpc-wKGJC52Uqn_nkQpMDLZPj0--15CzincUMiT-XtXe9zMDXpO4YBMKZcQs0TAIZkCk1lMqaQTchLCB0C_zeQxmTBGRQaZmJLXpcGmtaXVqrWuiVRjoq2qrBmProwat8UqCui7OqqV_0QfotL5CJWvdpGx6q1xwYaBYmNcja23Q-GUHJWqCni2X2fk5f7uefEYr54elovbVaw5gzZOjaR5oikFRk2aJ5LlKUjDjZQa14IbZEJQgJQxpTUTPEk5k2WZ6ZxDtubJjFyNfTfefXUY2qK2QWNVqQZdF4qcSpH096GX8Si1dyF4LIuNt_1Iu4JCMYRZjGEWY5i9v9h37tY1ml_9k14PLvdABa2q0qtG2_DnxPBblvfuenSu2_zz5jdipYyi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>916530070</pqid></control><display><type>article</type><title>Identification and validation of novel serum markers for early diagnosis of endometriosis</title><source>Oxford Journals Online</source><creator>Gajbhiye, R. ; Sonawani, A. ; Khan, S. ; Suryawanshi, A. ; Kadam, S. ; Warty, N. ; Raut, V. ; Khole, V.</creator><creatorcontrib>Gajbhiye, R. ; Sonawani, A. ; Khan, S. ; Suryawanshi, A. ; Kadam, S. ; Warty, N. ; Raut, V. ; Khole, V.</creatorcontrib><description>BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. METHODS A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. RESULTS The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. CONCLUSIONS Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.</description><identifier>ISSN: 0268-1161</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/der410</identifier><identifier>PMID: 22158085</identifier><identifier>CODEN: HUREEE</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Antibody Specificity ; Autoantibodies - analysis ; Autoantigens - blood ; Autoantigens - chemistry ; Biological and medical sciences ; Biomarkers - blood ; Biomarkers - chemistry ; Blood Proteins - chemistry ; Cohort Studies ; Cross-Sectional Studies ; Early Diagnosis ; Endometriosis - blood ; Endometriosis - diagnosis ; Endometriosis - physiopathology ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Immunodominant Epitopes - analysis ; Immunodominant Epitopes - chemistry ; Medical sciences ; Membrane Proteins - blood ; Membrane Proteins - chemistry ; Peptide Fragments - analysis ; Peptide Fragments - chemistry ; Peptide Mapping ; Sensitivity and Specificity ; Severity of Illness Index ; Tropomodulin - blood ; Tropomodulin - chemistry ; Tropomyosin - blood ; Tropomyosin - chemistry ; Young Adult</subject><ispartof>Human reproduction (Oxford), 2012-02, Vol.27 (2), p.408-417</ispartof><rights>The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</citedby><cites>FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25543729$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22158085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gajbhiye, R.</creatorcontrib><creatorcontrib>Sonawani, A.</creatorcontrib><creatorcontrib>Khan, S.</creatorcontrib><creatorcontrib>Suryawanshi, A.</creatorcontrib><creatorcontrib>Kadam, S.</creatorcontrib><creatorcontrib>Warty, N.</creatorcontrib><creatorcontrib>Raut, V.</creatorcontrib><creatorcontrib>Khole, V.</creatorcontrib><title>Identification and validation of novel serum markers for early diagnosis of endometriosis</title><title>Human reproduction (Oxford)</title><addtitle>Hum Reprod</addtitle><description>BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. METHODS A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. RESULTS The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. CONCLUSIONS Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.</description><subject>Adult</subject><subject>Antibody Specificity</subject><subject>Autoantibodies - analysis</subject><subject>Autoantigens - blood</subject><subject>Autoantigens - chemistry</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - chemistry</subject><subject>Blood Proteins - chemistry</subject><subject>Cohort Studies</subject><subject>Cross-Sectional Studies</subject><subject>Early Diagnosis</subject><subject>Endometriosis - blood</subject><subject>Endometriosis - diagnosis</subject><subject>Endometriosis - physiopathology</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunodominant Epitopes - analysis</subject><subject>Immunodominant Epitopes - chemistry</subject><subject>Medical sciences</subject><subject>Membrane Proteins - blood</subject><subject>Membrane Proteins - chemistry</subject><subject>Peptide Fragments - analysis</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Mapping</subject><subject>Sensitivity and Specificity</subject><subject>Severity of Illness Index</subject><subject>Tropomodulin - blood</subject><subject>Tropomodulin - chemistry</subject><subject>Tropomyosin - blood</subject><subject>Tropomyosin - chemistry</subject><subject>Young Adult</subject><issn>0268-1161</issn><issn>1460-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqF0D1PwzAQBmALgWgpjKwoC4Il9OzYTjKiio9KlVhgYIpc-wKGJC52Uqn_nkQpMDLZPj0--15CzincUMiT-XtXe9zMDXpO4YBMKZcQs0TAIZkCk1lMqaQTchLCB0C_zeQxmTBGRQaZmJLXpcGmtaXVqrWuiVRjoq2qrBmProwat8UqCui7OqqV_0QfotL5CJWvdpGx6q1xwYaBYmNcja23Q-GUHJWqCni2X2fk5f7uefEYr54elovbVaw5gzZOjaR5oikFRk2aJ5LlKUjDjZQa14IbZEJQgJQxpTUTPEk5k2WZ6ZxDtubJjFyNfTfefXUY2qK2QWNVqQZdF4qcSpH096GX8Si1dyF4LIuNt_1Iu4JCMYRZjGEWY5i9v9h37tY1ml_9k14PLvdABa2q0qtG2_DnxPBblvfuenSu2_zz5jdipYyi</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Gajbhiye, R.</creator><creator>Sonawani, A.</creator><creator>Khan, S.</creator><creator>Suryawanshi, A.</creator><creator>Kadam, S.</creator><creator>Warty, N.</creator><creator>Raut, V.</creator><creator>Khole, V.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Identification and validation of novel serum markers for early diagnosis of endometriosis</title><author>Gajbhiye, R. ; Sonawani, A. ; Khan, S. ; Suryawanshi, A. ; Kadam, S. ; Warty, N. ; Raut, V. ; Khole, V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Antibody Specificity</topic><topic>Autoantibodies - analysis</topic><topic>Autoantigens - blood</topic><topic>Autoantigens - chemistry</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - chemistry</topic><topic>Blood Proteins - chemistry</topic><topic>Cohort Studies</topic><topic>Cross-Sectional Studies</topic><topic>Early Diagnosis</topic><topic>Endometriosis - blood</topic><topic>Endometriosis - diagnosis</topic><topic>Endometriosis - physiopathology</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunodominant Epitopes - analysis</topic><topic>Immunodominant Epitopes - chemistry</topic><topic>Medical sciences</topic><topic>Membrane Proteins - blood</topic><topic>Membrane Proteins - chemistry</topic><topic>Peptide Fragments - analysis</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Mapping</topic><topic>Sensitivity and Specificity</topic><topic>Severity of Illness Index</topic><topic>Tropomodulin - blood</topic><topic>Tropomodulin - chemistry</topic><topic>Tropomyosin - blood</topic><topic>Tropomyosin - chemistry</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gajbhiye, R.</creatorcontrib><creatorcontrib>Sonawani, A.</creatorcontrib><creatorcontrib>Khan, S.</creatorcontrib><creatorcontrib>Suryawanshi, A.</creatorcontrib><creatorcontrib>Kadam, S.</creatorcontrib><creatorcontrib>Warty, N.</creatorcontrib><creatorcontrib>Raut, V.</creatorcontrib><creatorcontrib>Khole, V.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gajbhiye, R.</au><au>Sonawani, A.</au><au>Khan, S.</au><au>Suryawanshi, A.</au><au>Kadam, S.</au><au>Warty, N.</au><au>Raut, V.</au><au>Khole, V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and validation of novel serum markers for early diagnosis of endometriosis</atitle><jtitle>Human reproduction (Oxford)</jtitle><addtitle>Hum Reprod</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>27</volume><issue>2</issue><spage>408</spage><epage>417</epage><pages>408-417</pages><issn>0268-1161</issn><eissn>1460-2350</eissn><coden>HUREEE</coden><abstract>BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. METHODS A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. RESULTS The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. CONCLUSIONS Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22158085</pmid><doi>10.1093/humrep/der410</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0268-1161
ispartof Human reproduction (Oxford), 2012-02, Vol.27 (2), p.408-417
issn 0268-1161
1460-2350
language eng
recordid cdi_proquest_miscellaneous_916530070
source Oxford Journals Online
subjects Adult
Antibody Specificity
Autoantibodies - analysis
Autoantigens - blood
Autoantigens - chemistry
Biological and medical sciences
Biomarkers - blood
Biomarkers - chemistry
Blood Proteins - chemistry
Cohort Studies
Cross-Sectional Studies
Early Diagnosis
Endometriosis - blood
Endometriosis - diagnosis
Endometriosis - physiopathology
Female
Gynecology. Andrology. Obstetrics
Humans
Immunodominant Epitopes - analysis
Immunodominant Epitopes - chemistry
Medical sciences
Membrane Proteins - blood
Membrane Proteins - chemistry
Peptide Fragments - analysis
Peptide Fragments - chemistry
Peptide Mapping
Sensitivity and Specificity
Severity of Illness Index
Tropomodulin - blood
Tropomodulin - chemistry
Tropomyosin - blood
Tropomyosin - chemistry
Young Adult
title Identification and validation of novel serum markers for early diagnosis of endometriosis
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T03%3A37%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20and%20validation%20of%20novel%20serum%20markers%20for%20early%20diagnosis%20of%20endometriosis&rft.jtitle=Human%20reproduction%20(Oxford)&rft.au=Gajbhiye,%20R.&rft.date=2012-02-01&rft.volume=27&rft.issue=2&rft.spage=408&rft.epage=417&rft.pages=408-417&rft.issn=0268-1161&rft.eissn=1460-2350&rft.coden=HUREEE&rft_id=info:doi/10.1093/humrep/der410&rft_dat=%3Cproquest_cross%3E916530070%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=916530070&rft_id=info:pmid/22158085&rft_oup_id=10.1093/humrep/der410&rfr_iscdi=true